Research Article

Autophagy in combination therapy of temozolomide and IFN-γ in C6-induced glioblastoma: role of non-coding RNAs

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran

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Maryam Moazam-Jazi

Cellular & Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, 19857-17413, Iran

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Mohammad Reza Karimzadeh

Department of Medical Genetics, School of Medicine, Bam University of Medical Sciences, Bam, 76198-13159, Iran

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Saeideh Jafarinejad-Farsangi

*Author for correspondence: Tel.: +98 343 222 4990;

E-mail Address: s.jafarinejad@kmu.ac.ir

https://orcid.org/0000-0003-4694-8174

Student Research Committee, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran

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Amirhossein Moslemizadeh

Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran

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Marziyeh Lotfian

Endocrinology & Metabolism Research Center, Institute of Basic & Clinical Physiology Sciences, Kerman University of Medical Sciences Kerman, 76198-13159, Iran

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Zahra Miri Karam

Cardiovascular Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran

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Reza Kheirandish

Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, 76198-13159, Iran

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Mohammad Mojtaba Farazi

Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, 76198-13159, Iran

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Published Online:16 Aug 2023https://doi.org/10.2217/imt-2022-0212

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Abstract

Aim: We predicted the modulation of autophagy and apoptosis in response to temozolomide (TMZ) and IFN-γ based on changes in the expression of non-coding RNAs in C6-induced glioblastoma (GBM). Materials & methods: Each rat received an intraperitoneal injection of TMZ (7.5 mg/kg) and/or IFN-γ (50,000 IU). Results: The reduced expression of H19 and colorectal neoplasia differentially expressed (CRNDE) was associated with a reduction in autophagy in response to TMZ, IFN-γ and TMZ + IFN-γ therapy, whereas the decreased level of miR-29a (proapoptotic miRNA) was associated with an increase in apoptosis. Conclusion: It appears that H19 promotes switching from autophagy to apoptosis in response to combination therapy of TMZ and IFN-γ through the miR-29a/autophagy-related protein 9A (ATG9A) pathway in C6-induced GBM.

Plain language summary

Temozolomide (TMZ) is a drug for people with brain cancer. It can make it hard for patients to learn and think, and it can also make the drug stop working, which lets the tumor keep growing. Researchers are looking for other drugs or things that can be taken with TMZ to stop this from happening. In this study, we used a protein called interferon (IFN), which helps fight cancer. We gave mice with brain cancer both TMZ and IFN, and saw that the tumor cells died and the tumor got smaller. We also looked at how IFN and TMZ changed the genetic material of the mouse brain, called RNA. But we need to test this on people to be sure it works.

Tweetable abstract

TMZ in combination with IFN-γ switched autophagy to apoptosis in C6-induced GBM in rats through H19/miR-29a/ATG9A axis.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 14

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History

Received 23 August 2022

Accepted 7 July 2023

Published online 16 August 2023

Published in print October 2023

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Keywords

Author contributions

S Jafarinejad-Farsangi and H Bashiri designed the research. AH Moslemizadeh and R Kheirandish established the animal model. M Moazam Jazi, M Lotfian, Z Miri Karam, MM Farazi and MR Karimzadeh conducted the experiments. S Jafarinejad-Farsangi and R Kheirandish analyzed the data. S Jafarinejad-Farsangi and H Bashiri wrote the manuscript. All authors read and approved the final version of the manuscript.

Financial & competing interests disclosure

This work was supported by a grant received by S Jafarinejad-Farsangi from the student research committee, Kerman University of Medical Sciences, Kerman, Iran (grant no. 40000456). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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